Genetic analysis of spontaneous animal model of neurodegeneration to study molecular mechanisms underlying selective regional vulnerability
Project/Area Number |
18590396
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
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Research Institution | Institute for Developmental Research, Aichi Human Service Center |
Principal Investigator |
SHIMADA Atsuyoshi Institute for Developmental Research, Aichi Human Service Center, 病理学部, 室長 (50311444)
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Co-Investigator(Kenkyū-buntansha) |
細川 昌則 愛知県心身障害者コロニー発達障害研究所, 病理学部, 部長 (00127135)
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Project Period (FY) |
2006 – 2008
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Project Status |
Completed (Fiscal Year 2008)
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Budget Amount *help |
¥4,100,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥600,000)
Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
Keywords | 神経変性 / ユビキチン / プロテアソーム / 疾患モデル動物 / 封入体 / 脳 / 老化 / 連鎖解析 / 加齢 / QTL / 量的形質 / コンジェニック / 近交系 / プロテオーム / 中間径フィラメント / インターネキシン / 大脳辺縁系 / マウス / モデル |
Research Abstract |
神経変性疾患では特定の脳領域に変性が進行する傾向があるが、そのメカニズムは不明である。ここでは、ニューロン変性が加齢に伴って大脳辺縁系に選択的に進行するSAMP10マウスを神経変性のモデルとして解析した結果、神経変性の原因として、タンパク質分解系であるプロテアソーム活性の低下、軸索を構築する主要な細胞骨格タンパク質であるα-internexinのリン酸化の亢進が重要であることがわかった。神経変性の原因遺伝子については、15番染色体の特定の領域に存在することは突き止めたものの、同定にはさらなる研究が必要である。
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Report
(4 results)
Research Products
(85 results)
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[Journal Article] Falls in adults with intellectual disability : risk factors and risk assessment2009
Author(s)
Chiba, Y., Shimada, A., Yoshida, F., Keino, H., Hasegawa, M., Miyake, S., Ikari, H., Hosokawa, M
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Journal Title
Am J Intellectual and Developmental Disabilities 114
Pages: 225-236
Related Report
Peer Reviewed
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[Journal Article] The Senescence-accelerated Mouse (SAM) : a higher oxidative stress and agedependent degenerative diseases model2009
Author(s)
Chiba, Y., Shimada, A., Kumagai, N., Yoshikawa, K., Ishii, S., Furukawa, A. Takei, S., Sakura M., Kawamura, N., Hosokawa, M.
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Journal Title
Neurochem. Res. 34
Pages: 679-87
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Peer Reviewed
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[Journal Article] The Senescence-accelerated Mouse (SAM) : a higher oxidative stress and age-dependent degenerative diseases model2009
Author(s)
Chiba, Y., Shimada, A., Kumagai, N., Yoshikawa, K., Ishii, S., Furukawa, A., Takei, S., Sakura M., Kawamura, N., Hosokawa, M.
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Journal Title
Neurochem. Res. 34
Pages: 679-687
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Peer Reviewed
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[Journal Article] Falls in adults with intellectual disability : risk factors and risk assessment. Am J Intellectual and Developmental Disabilities (formerly Am J Mental Retard) ^*corresponding author2009
Author(s)
Chiba, Y., Shimada, A.^*, Yoshida, F., Keino, H., Hasegawa, M., Miyake, S., Ikari, H., Hosokawa, M.
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Journal Title
American Journal of Intellectual and Developmental Disabilities 114
Pages: 225-236
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Peer Reviewed
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[Journal Article] Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-accelerated mouse strain P82008
Author(s)
Komatsu, T., Chiba, T., Yamaza, H., Yamashita, K., Shimada, A., Hoshiyama, Y., Henmi, T., Otani, H., Higami, Y., Ingram, D. K., Shimokawa, I.
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Journal Title
Exp. Gerontol. 43
Pages: 339-346
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Peer Reviewed
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[Journal Article] Neuronal toxicity of expanded polyglutamine depends on intracellular distribution in addition to the expression level2008
Author(s)
Satoh, M., Shimada, A., Kawamura, N. Chiba, Y., Yoshikawa K., Ishii, S., Furukawa, A., Kumagai, N., Hosokawa, M.
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Journal Title
Neuropathology 28
Pages: 485-496
NAID
Related Report
Peer Reviewed
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[Journal Article] Reduced expression of MAb6B4 epitopes on chondroitin sulfate proteoglycan aggrecan in perineuronal nets from the cerebral cortices of SAMP10 mice : A model for age-dependent neurodegeneration2008
Author(s)
Saitoh, Y., Matsui, F., Chiba, Y., Kawamura, N., Keino, H., Satoh, M., Kumagai, N., Ishii, S., Yoshikawa, K., Shimada, A., Maeda, N., Oohira, A., Hosokawa, M.
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Journal Title
J. Neurosci. Res. 86
Pages: 1316-1323
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Peer Reviewed
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[Journal Article] Age-related increase of superoxide generation in the brains of mammals and birds2008
Author(s)
Sasaki, T., Unno, K., Tahara, S., Shimada, A., Chiba, Y., Hoshino, M., Kaneko, T.
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Journal Title
Aging Cell 7
Pages: 459-469
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Peer Reviewed
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[Journal Article] Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-accelerated mouse strain P8.2008
Author(s)
Komatsu, T., Chiba, T., Yamaza, H., Yamashita, K., Shimada, A., Hoshiyama, Y., Henmi, T., Otani, H., Higami, Y., Ingram, D.K., and Shimokawa, I.
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Journal Title
Experimental Gerontology 43
Pages: 339-346
Related Report
Peer Reviewed
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[Journal Article] Neuronal toxicity of expanded polyglutamine depends on intracellular distribution in addition to the expression level.2008
Author(s)
Satoh, M., Shimada, A., Kawamura, N., Chiba, Y., Yoshikawa, K., Ishii, S., Furukawa, A., Kumagai, N., and Hosokawa, M.
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Journal Title
NAID
Related Report
Peer Reviewed
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[Journal Article] Age-related increase of superoxide generation in the brains of mammals and birds.2008
Author(s)
Sasaki, T., Unno, K., Tahara, S., Shimada, A., Chiba, Y., Hoshino, M., and Kaneko, T.
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Reduced expression of MAb6B4-epitopes on chondroitin sulfate proteoglycan aggrecan in perineuronal nets from the cerebral cortices of SAMP10 mice, a model for age-dependent neurodegeneration.2008
Author(s)
Saitoh, Y., Matsui, F., Chiba, Y., Kawamura, N., Keino, H., Satoh, M., Kumagai, N., Ishii, S., Yoshikawa, K., Shimada, A., Maeda, N., Oohira, A., and Hosokawa, M.
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Journal Title
Journal of Neuroscience Research (印刷中)
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Peer Reviewed
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[Journal Article] Involvement of pro-inflammatory cytokines and microglia in an age-associated neurodegeneration model the SAMP10 mouse2007
Author(s)
Kumagai, N., Chiba, Y., Hosono, Fujii, M., Kawamura, N., Keino, H., Yoshikawa, K., Ishii, S., Saitoh, Y., Satoh, M., Shimada, A., Hosokawa, M.
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Journal Title
Brain Res. 1185
Pages: 75-85
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Peer Reviewed
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[Journal Article] Involvement of pro-inflammatory cytokines and microglia in an age-associated neurodegeneration model, the SAMP10 mouse.2007
Author(s)
Kumagai, N., Chiba, Y., Hosono, M., Fujii, M., Kawamura, N., Keino, H., Yoshikawa, K., Ishii, S., Saitoh, Y., Satoh, M., Shimada, A., and Hosokawa, M.
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Journal Title
Brain Research 1185
Pages: 75-85
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Peer Reviewed
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[Journal Article] Apical vulnerability to dendritic retraction in prefrontal neurones of ageing SAMP10 mouse : a model of cerebral degeneration2006
Author(s)
Shimada, A., Tsuzuki, M., Keino, H., Satoh, M., Chiba, Y., Saitoh, Y., Hosokawa, M.
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Journal Title
Neuropathol. Appl. Neurobiol. 32
Pages: 1-14
Related Report
Peer Reviewed
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[Journal Article] Expression and identification of a new splice variant of neuroglycan C, a transmembrane chondroitin sulfate proteoglycan, in the human brain2006
Author(s)
Aono, S., Tokita, Y., Yasuda, Y., Hirano, K., Yamauchi, S., Shuo, T., Matsui, F., Keino, H., Kashiwai, A., Kawamura, N., Shimada, A., Kishikawa, M. Asai, M., Oohira, A.
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Journal Title
J. Neurosci. Res. 83
Pages: 110-118
Related Report
Peer Reviewed
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[Journal Article] Effects of aging and HIF-1α deficiency on permeability of hippocampal vessels2006
Author(s)
Ueno, M., Tomita, S., Nakagawa, T., Ueki, M., Iwanaga, Y., Ono, J., Onodera, M., Huang, C.L., Kanenishi, K., Shimada, A., Maekawa, N., Sakamoto, H.
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Journal Title
Microsc. Res. Tech. 69
Pages: 29-35
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Peer Reviewed
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[Journal Article] Sensory system-predominant distribution of leukotriene A_4 hydrolase and its colocalization with calretinin in the mouse nervous system2006
Author(s)
Chiba, Y., Shimada, A., Satoh. M., Saitoh, Y., Kawamura, N., Hanai, A., Keino, H., Ide, Y., Shimizu, T., Hosokawa, M.
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Journal Title
Neuroscience 141
Pages: 917-927
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[Presentation] SAMP10マウス大脳皮質におけるプロテオグリカン関連エピトープ6B4の発現低下2007
Author(s)
松井ふみ子, 齊藤優子, 河村則子, 慶野裕美, 千葉陽一, 熊谷直子, 石井さなえ, 吉川圭介, 島田厚良, 前田信明, 大平敦彦, 細川昌則
Organizer
第30回日本神経科学大会
Place of Presentation
横浜市
Year and Date
2007-09-10
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[Presentation] 加齢に伴うミクログリアの退行性変化2007
Author(s)
石井さなえ, 島田厚良, 千葉陽一, 吉川圭介, 古川絢子, 河村則子, 熊谷直子, 細川昌則
Organizer
第22回老化促進モデルマウス(SAM)研究協議会
Place of Presentation
酒田市
Year and Date
2007-07-27
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[Presentation] SAMP10におけるFgf1遺伝子異常の確認とその機能的意義の検討2006
Author(s)
長谷川さなえ, 島田厚良, 梅垣宏行, 井口昭久, 慶野裕美, 河村則子, 吉川圭介, 佐藤衛, 千葉陽一, 斉藤優子, 熊谷直子, 細川昌則
Organizer
第21回老化促進モデルマウス(SAM)研究協議会
Place of Presentation
名古屋市
Year and Date
2006-07-27
Related Report
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[Presentation] SAMP10マウス脳における神経細胞周囲網の異常2006
Author(s)
斉藤優子, 松井ふみ子, 河村則子, 慶野裕美, 熊谷直子, 吉川圭介, 長谷川さなえ、佐藤衛, 千葉陽一, 島田厚良, 前田信明, 大平敦彦, 細川昌則
Organizer
第21回老化促進モデルマウス(SAM)研究協議会
Place of Presentation
名古屋市
Year and Date
2006-07-27
Related Report
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[Presentation] モデルマウスを用いた中枢神経細胞の加齢変性におけるneuroinflammationの役割の検討-ミクログリアの加齢変化2006
Author(s)
熊谷直子, 千葉陽一, 島田厚良, 細野正道, 藤井庄人, 佐藤衛, 斉藤優子, 河村則子, 慶野裕美, 吉川圭介, 長谷川さなえ, 細川昌則
Organizer
第21回老化促進モデルマウス(SAM)研究協議会
Place of Presentation
名古屋市
Year and Date
2006-07-27
Related Report
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[Presentation] SAMP10の脳における脂質メディエーターの産生プロファイリング2006
Author(s)
吉川圭介, 島田厚良, 長谷川さなえ, 北芳博, 清水孝雄, 河村則子, 佐藤衛, 千葉陽一, 慶野裕美, 熊谷直子, 斉藤優子, 細川昌則
Organizer
第21回老化促進モデルマウス(SAM)研究協議会
Place of Presentation
名古屋市
Year and Date
2006-07-27
Related Report
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